Synergy of sequential administration of a deglycosylated ricin A chain-containing combined anti-CD19 and anti-CD22 immunotoxin (Combotox) and cytarabine in a murine model of advanced acute lymphoblastic leukemia

Stefan K. Barta, Yiyu Zou, John Schindler, Niraj Shenoy, Tushar D. Bhagat, Ulrich Steidl, Amit Verma

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The outcome for patients with refractory or relapsed acute lymphoblastic leukemia (ALL) treated with conventional therapy is poor. Immunoconjugates present a novel approach and have recently been shown to have efficacy in this setting. Combotox is a mixture of two ricin-conjugated monoclonal antibodies (RFB4 and HD37) directed against CD19 and CD22, respectively, and has shown activity in pediatric and adult ALL. We created a murine xenograft model of advanced ALL using the NALM/6 cell line to explore whether the combination of Combotox with the cytotoxic agent cytarabine (Ara-C) results in better outcomes. In our model the combination of both low- and high-dose Combotox and Ara-C resulted in significantly longer median survival. Sequential administration of Ara-C and Combotox, however, was shown to be superior to concurrent administration. These findings have led to a phase I clinical trial exploring this combination in adults with relapsed or refractory B-lineage ALL (ClinicalTrials.gov identifier NCT01408160).

Original languageEnglish (US)
Pages (from-to)1999-2003
Number of pages5
JournalLeukemia and Lymphoma
Volume53
Issue number10
DOIs
StatePublished - Oct 1 2012

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Keywords

  • Acute lymphoblastic
  • Animal model
  • Cytarabine
  • Immunoconjugate
  • Leukemia
  • Mouse
  • NOD
  • Ricin

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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